1. Field of the Invention
The present invention relates to a 2H-indazole derivative, more precisely to a 2-methyl-indazole derivative.
2. Description of the Prior Art
Clonidine (INN for 2-((2,6-dichloro-phenyl)-imino)-imidazolidine) and Phenoxybenzamine (INN for N-benzyl-N-(2-chloroethyl)-N-(1-methyl-2-phenoxy-ethyl)-amine) rank amongst the most valuable anti-hypertensives. Both are in use as drugs. Nevertheless, both have significant drawbacks, especially as to side-effects and contra-indications. Clonidine is an .alpha..sub.2 -agonist, i.e. it has stimulating agonist activity on the prejunctional .alpha..sub.2 -adrenoceptors, especially those in the medulla oblongata. Clonidine thus penetrates the blood-brain barrier for central anti-hypertensive action.
Phenoxybenzamine in contrast is an .alpha..sub.2 -adrenoceptor antagonist at higher concentration and a very effective .alpha..sub.1 -adrenoceptor blocker already at lower concentration. Nevertheless, phenoxybenzamine, too, readily penetrates the blood-brain barrier.
In consequence, regardless of their valuable anti-hypertensive activity, both, clonidine and phenoxybenzamine, show significant side-effects such as a central nervous system depression (sedation, prostration and hyporeactivity) tachycardic reaction and orthostatic regulation disturbance.
Finally, a series of 1H-indazole derivatives is disclosed in the U.S. Pat. Nos. 3,847,934 and 4,036,976. To applicants' best knowledge none of said prior art 1H-indazole derivatives is in commercial use as a drug. The most anti-hypertensively active species out of said 1H-indazoles is the compound 4-(2-imidazolin-2-yl-amino)-1-methyl-indazole as disclosed in U.S. Pat. No. 4,036,976.
Having a therapeutic index LD.sub.50 /ED.sub.50 in the range of 400 (nephrogenic GOLDBLATT-hypertensive rats, p.o.) to 800 (genetically fixed hypertension rats, p.o.), the 4-(2-imidazolin-2-yl-amino)-1-methyl-indazole shows an activity and a therapeutic range comparable to the corresponding data for clonidine. However, obviously also the aforementioned 1-methyl-indazole derivative penetrates the blood-brain barrier, and thus causes similar side-effects as discussed above.